{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:38:46Z","timestamp":1790786326696,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T00:00:00Z","timestamp":1660608000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The catalytic subunit of polycomb repressive complex 2 (PRC2), enhancer of zeste homolog 2 (EZH2), has been reported to be involved in angiogenesis in some tumors and autoimmune diseases. However, the mechanisms by which EZH2 regulates peritoneal angiogenesis remain unclear. We detected the expression of EZH2 in clinical samples and the peritoneal tissue of a mouse peritoneal fibrosis model induced by chlorhexidine gluconate (CG). In addition, we further investigated the mechanisms by which inhibition of EZH2 by 3\u2010deazaneplanocin A (3\u2010DZNeP) alleviated the CG\u2010induced peritoneal fibrosis mouse model <jats:italic>in vivo<\/jats:italic> and 3\u2010DZNeP or EZH2 siRNA treatment in cultured human peritoneal mesothelial cells (HPMCs) and human umbilical vein endothelial cells (HUVECs). The expression of EZH2 in the peritoneum of long\u2010term peritoneal dialysis (PD) patients and the CG\u2010induced peritoneal fibrosis mouse model was remarkably increased and this was positively associated with higher expression of vascular markers (CD31, CD34, VEGF, p\u2010VEGFR2). Peritoneal injection of 3\u2010DZNeP attenuated angiogenesis in the peritoneum of CG\u2010injured mice; improved peritoneal membrane function; and decreased phosphorylation of STAT3, ERK1\/2, and activation of Wnt1\/\u03b2\u2010catenin. In <jats:italic>in vitro<\/jats:italic> experiments, we demonstrated that inhibition of EZH2 by 3\u2010DZNeP or EZH2 siRNA decreased tube formation and the migratory ability of HUVECs via two pathways: the Wnt1\/\u03b2\u2010catenin pathway and the IL\u20106\/STAT3 pathway. Suppression of the Wnt1\/\u03b2\u2010catenin pathway and the IL\u20106\/STAT3 pathway subsequently reduced VEGF production in HPMCs. Using specific inhibitors of VEGFR2, ERK1\/2, and HIF\u20101\u03b1, we found that a VEGFR2\/ERK1\/2\/HIF\u20101\u03b1 axis existed and contributed to angiogenesis <jats:italic>in vitro<\/jats:italic>. Moreover, phosphorylation of VEGFR2 and activation of the ERK1\/2 pathway and HIF\u20101\u03b1 in HUVECs could be suppressed by inhibition of EZH2. Taken together, the results of this study suggest that EZH2 may be a novel target for preventing peritoneal angiogenesis in PD patients. \u00a9 2022 The Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.5987","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T09:21:41Z","timestamp":1657099301000},"page":"164-178","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Inhibition of <scp>EZH2<\/scp> suppresses peritoneal angiogenesis by targeting a <scp>VEGFR2<\/scp>\/<scp>ERK1<\/scp>\/2\/<scp>HIF<\/scp>\u20101\u03b1\u2010dependent signaling pathway"],"prefix":"10.1002","volume":"258","author":[{"given":"Yingfeng","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Nephrology, Shanghai East Hospital Tongji University School of Medicine  Shanghai PR 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